RT Journal Article
SR Electronic
T1 The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.23.445310
DO 10.1101/2021.05.23.445310
A1 Ajit J. Nirmal
A1 Zoltan Maliga
A1 Tuulia Vallius
A1 Brian Quattrochi
A1 Alyce A. Chen
A1 Connor A. Jacobson
A1 Roxanne J. Pelletier
A1 Clarence Yapp
A1 Raquel Arias-Camison
A1 Yu-An Chen
A1 Christine G. Lian
A1 George F. Murphy
A1 Sandro Santagata
A1 Peter K. Sorger
YR 2022
UL http://biorxiv.org/content/early/2022/02/14/2021.05.23.445310.abstract
AB Cutaneous melanoma is a highly immunogenic malignancy, surgically curable at early stages, but life- threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially-resolved micro-region transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis involving precursor states, melanoma in situ, and invasive tumor. Hallmarks of immunosuppression are already detectable in precursor regions. When tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor-stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1, and by PD1-PDL1 mediated cell contacts involving macrophages, dendritic cells, and T cells. A few millimeters away, cytotoxic T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can co-exist within a few millimeters of each other in a single specimen.STATEMENT OF SIGNIFICANCE The reorganization of the tumor ecosystem in primary melanoma is an excellent setting in which to study immunoediting and immune evasion. Guided by classical histopathology, spatial profiling of proteins and mRNA reveals recurrent morphological and molecular features of tumor evolution that involve localized paracrine cytokine signaling and direct cell-cell contact.Competing Interest StatementPKS is a member of the SAB or Board of Directors of Glencoe Software, Applied Biomath, and RareCyte Inc. and has equity in these companies; PKS is also a member of the SAB of NanoString and a consultant for Montai Health and Merck. Glencoe, RareCyte, and NanoString provided commercially-available technology used in this study. SS is a consultant for RareCyte Inc. ZM is a consultant for Verseau Therapeutics Inc. The authors declare that none of these relationships have influenced the content of this manuscript.